Organometallic Ru, Os, Rh and Ir half-sandwich conjugates of ispinesib – impact of the organometallic group on the antimitotic activity

Łomzik, Michał; Błauż, Andrzej; Głodek, Marta; Makal, Anna; Tchoń, Daniel; Ayine-Tora, Daniel Moscoh; Hartinger, Christian G.; Rychlik, Błażej; Plażuk, Damian

doi:10.1039/d3dt01217d

Cited by 3 publications

(3 citation statements)

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“…Structure of (a) ispinesib, (b) its quinazoline-derived Ru, Os, Rh, and Ir half-sandwich conjugates reported previously, , and (c) compounds studied herein.…”

Section: Introductionmentioning

confidence: 99%

“…Organometallic conjugates often exhibit stronger antiproliferative properties than parent compounds and, in many cases, exhibit additional biological properties. In recent Structure of (a) ispinesib, (b) its quinazoline-derived Ru, Os, Rh, and Ir half-sandwich conjugates reported previously, 44,45 and (c) compounds studied herein.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Recently, we have reported the synthesis and biological evaluation of a series of ferrocenyl and Ru, Os, Rh, and Ir half-sandwich , conjugates of ispinesib and its 7-chloroquinazolin-4(3H)-one core. Continuing our study on novel organometallic antimitotic agents, we designed new half-sandwich complexes derived from the ispinesib core.…”

Section: Introductionmentioning

confidence: 99%

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Development of Half-Sandwich Ru, Os, Rh, and Ir Complexes Bearing the Pyridine-2-ylmethanimine Bidentate Ligand Derived from 7-Chloroquinazolin-4(3H)-one with Enhanced Antiproliferative Activity

Łomzik,

Błauż,

Tchoń

et al. 2024

ACS Omega

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Kinesin spindle protein (KSP) inhibitors are one of the most promising anticancer agents developed in recent years. Herein, we report the synthesis of ispinesib-core pyridine derivative conjugates, which are potent KSP inhibitors, with half-sandwich complexes of ruthenium, osmium, rhodium, and iridium. Conjugation of 7-chloroquinazolin-4(3H)-one with the pyridine-2-ylmethylimine group and the organometallic moiety resulted in up to a 36-fold increased cytotoxicity with IC 50 values in the micromolar and nanomolar range also toward drug-resistant cells. All studied conjugates increased the percentage of cells in the G 2 / M phase, simultaneously decreasing the number of cells in the G 1 / G 0 phase, suggesting mitotic arrest. Additionally, ruthenium derivatives were able to generate reactive oxygen species (ROS); however, no significant influence of the organometallic moiety on KSP inhibition was observed, which suggests that conjugation of a KSP inhibitor with the organometallic moiety modulates its mechanism of action.

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“…Structure of (a) ispinesib, (b) its quinazoline-derived Ru, Os, Rh, and Ir half-sandwich conjugates reported previously, , and (c) compounds studied herein.…”

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%